In 2022, Mental-health Clinic No. 4 named after P. B. Gannushkin, one of the oldest mental health institutions in Russia known as Preobrazhenskaya Hospital before the October Revolution of 1917, celebrated its 245th anniversary. The history of the hospital reflects all stages of the evolution of the basic principles and aspects of mental health care in Russia. On many occasions, the institution served as a platform for eminent researchers and clinicians to achieve scientific breakthroughs and their application in practice. This article is a review of the major milestones in the history of the hospital. It highlights the great achievements of its psychiatrists and presents some previously unpublished archival documents that offer a new perspective on the history of Preobrazhenskaya Hospital.